Immune Support: Quercetin, Vitamin C, Zinc, Vitamin D3 (2024)

Doctors and pharmacists have been overwhelmed with questions about the use of supplements, OTC (Over The Counter) medications, and prescription drugs in the battle against the virus that causes COVID-19. While the best evidence continues to support behaviors like maintaining a physical distance of 6 feet, wearing a mask, and washing hands frequently and thoroughly—research indicates that certain supplements and common OTC medications could reduce the risk of infection or mitigate the seriousness of symptoms.

The Front Line COVID-19 Critical Care Alliance (FLCCC) and other healthcare organizations have incorporated a mix of readily available agents into their management protocol for COVID-19.

1. Vitamin D3 - Anti-inflammatory and Anti-coagulant

At this point, there is simply no question that vitamin D optimization is a crucial component of COVID-19 prevention and treatment. In addition to the many studies published during 2020 and 2021, since December 2021, four large systematic meta-analyses (R, R, R, R) have been published, looking at either vitamin D levels, supplementation or both.

A meta-analysis of randomized controlled trials, published in Pharmaceuticals (Jan 2023), is titled “Protective Effect of Vitamin D Supplementation on COVID-19-Related Intensive Care Hospitalisation and Mortality: Definitive Evidence from Meta-Analysis and Trial Sequential Analysis”. Vitamin D cuts the risk of death from COVID-19 by 51% and the risk of ICU admission by 72%.

In all cases, the data consistently show that low vitamin D levels raises your risk of COVID while higher baseline levels and/or supplementation lowers all risks by 1.5 to three times.

The TSA (trial sequential analysis) revealed "the protective role of vitamin D and ICU admission showed that, since the pooling of the studies reached a definite sample size, the positive association is conclusive." To put it another way, the results suggest "a definitive association between the protective role of vitamin D and ICU hospitalization." 

Words like "conclusive" and "definitive" aren't typically used lightly in scientific research. So, this finding is indeed impressive — although not altogether surprising, since a wealth of other data also shows vitamin D's protective effect against COVID-19. What does raise eyebrows, however, is why the study, which has major implications for public health, isn't being talked about — and vitamin D isn't being widely recommended for COVID-19?

Vitamin D, as an immuno-modulator, is a perfect candidate for countering the immune dysregulation common with COVID-19. Vitamin D deficiency affects the body’s susceptibility to infection and has been associated with influenza, hepatitis C, human immunodeficiency virus (HIV) and other viral diseases [Source]. Surveys indicate that most people in the United States consume less than recommended amounts of vitamin D. 

Scientists from Harvard reported in 2021 that hospitalized patients with a 'Vitamin D blood serum level' of ≥30ng/mL had a much lower mortality rate than those with <30ng/mL.

Results of a systematic review and meta-analysis (Nutrients 2021) suggested that COVID-19 mortality risk correlates inversely with vitamin D3 status, and a mortality rate close to zero could theoretically be achieved at 50 ng/ml 25(OH)D3.

In a June 2022 review paper titled “The Role of Diet and Supplements in the Prevention and Progression of COVID-19: Current Knowledge and Open Issues”​ published in the journal Preventive Nutrition and Food Science, researchers said:

"The consumption of vitamin C and D supplements, in addition to a healthy diet, could be promoted as a co-adjuvant therapy for COVID-19..."

For more evidence, check out the evidence tracker on vitamin D and COVID-19 from c19vitamind.com (constantly updated), with more than 100 published treatment studies and more than 130 sufficiency studies by more than 1,000 scientists.

Trusted Source

Vitamin D has also been shown to have an anticoagulant effect. A decrease in 25-hydroxyvitamin D [25(OH)D] concentration has also been associated with an increased risk of venous thromboembolism (PubMed).

Safety: Daily intakes of up to 25–100 mcg (1,000 IU–4,000 IU) vitamin D in foods and dietary supplements are safe for children (depending on their age) and up to 100 mcg (4,000 IU) are safe for adults. These values, however, do not apply to individuals receiving vitamin D treatment under the care of a physician. Higher intakes (usually from supplements) can lead to nausea, vomiting, muscle weakness, confusion, pain, loss of appetite, dehydration, excessive urination and thirst, and kidney stones. In extreme cases, vitamin D toxicity causes renal failure, calcification of soft tissues throughout the body (including in coronary vessels and heart valves), cardiac arrhythmias, and even death.

Excessive vitamin D in combination with lack of vitamin K2 may cause over-absorption of calcium, which in turn may result in calcium deposits in your heart and kidneys and why some experience symptoms of vitamin D toxicity. Part of the explanation for these adverse side effects is that vitamin K2 keeps calcium in its appropriate place — in your teeth and bones and out of soft tissues and arteries.

Vitamin D and Omicron variants

Will Vitamin D Work Against Omicron BA4, BA 5 and XBB variants? Vitamin D is not variant specific because it's primary mode of action is to support the body’s immune system which reacts in a variety of ways against viral attack, not just in a specific antibody reaction to a specific spike protein. 

Related: Best Vitamin D3 Supplement

2. Quercetin - Anti-inflammatory, anti-coagulant, zinc ionophore and anti-viral

As of April 2024, there have been 11 published studies of quercetin and COVID-19 (c19quercetin.com). 

Quercetin is a pigment that is found in plants, vegetables, and fruits, and serves as an immune nutrient offering many health benefits. Elderberry, red onions, white onions and cranberries are the richest sources of quercetin. It is a flavonoid and antioxidant that may help to reduce inflammatory cytokines, infections, allergies and anti-blood clot property. Research has found that quercetin may be particularly beneficial for viral respiratory infections.

Quercetin as a Zinc Ionophore

Quercetin is a zinc ionophore (J Agric Food Chem. 2014). A 2015 study found that that Quercetin shows inhibitory activity in the early stages of a wide range of influenza viruses, including H1N1 and H5N1 (Viruses 2016). Although influenza is not in the same family of viruses as the coronavirus, it’s plausible that a similar mechanism could apply here. There is actually some evidence that Quercetin has already proven effective at treating Ebola and Zika viruses.

Quercetin and Vitamin C

Incidentally, ascorbic acid (vitamin C) and the bioflavonoid quercetin (originally labeled vitamin P) were both discovered by the same scientist — Nobel prize winner Albert Szent-Györgyi. Quercetin and vitamin C also act as an antiviral drug, effectively inactivating viruses. 

Quercetin Dosage

The FLCCC I-MASK+ protocol recommends 250 mg daily for prevention and 250 mg twice daily for early treatment.

Quercetin works best when taken with vitamin C and Bromelain, as vitamin C helps activate it and bromelain helps with the absorption.

Precaution: Quercetin should be used with caution in patients with hypothyroidism (low thyroid hormone) and relevant thyroid hormone levels should be monitored.

Quercetin and ivermectin interactions? According to Drugs.com: "No interactions were found between ivermectin and Quercetin. This does not necessarily mean no interactions exist. Always consult your healthcare provider."

Quercetin and COVID-19

For an updated list of studies, check out c19quercetin.com. 

A word about quercetin: Some physicians are recommending this supplement to reduce viral illnesses because quercetin acts as a zinc ionophore to improve zinc uptake into cells. It is much less potent than HCQ (hydroxychloroquine) as a zinc transporter, and it does not reach high concentrations in lung cells that HCQ does. Quercetin may help reduce risk of viral illness if you are basically healthy. But it is not potent enough to replace HCQ for treatment of COVID once you have symptoms, and it does not adequately get into lung tissue unless you take massive doses (3-5 grams a day), which cause significant GI (gastrointestinal) side effects such as diarrhea.

Editor's Note: Studies typically use advanced formulations for greatly improved bioavailability.

Related: Best Quercetin Zinc Supplement

3. Zinc - Anti-viral 

Zinc is another powerful immune nutrient known for its benefits for providing immune health support and inflammation reduction as well as for improving cold and respiratory symptoms, wound healing, acne reduction, and lowering the risk of age-related diseases. This trace element is essential to to cell function and involved in over 100 enzymes. Research on atherosclerosis and diabetes mellitus suggests that zinc deficiency may contribute to low-grade systemic inflammation.

Aging is associated with compromised immunity, that just means that your immune response to pathogens and infections starts to slow and is less robust, including a reduced vaccine immune response/efficacy. ⁣
⁣
Improving zinc intake/zinc status improves/modulates/enhances immune function. The flip side is, while some aspects of immunity slow, others increase. Uncontrolled immune responses drive excess inflammation. Zinc helps to balance all of this. ⁣

The National Institutes of Health (NIH) states:

“Zinc is involved in numerous aspects of cellular metabolism. It is required for the catalytic activity of approximately 100 enzymes and it plays a role in immune function, protein synthesis, wound healing, DNA synthesis, and cell division. Zinc also supports normal growth and development during pregnancy, childhood, and adolescence and is required for proper sense of taste and smell.”

Foods that are high in zinc include oysters, crab, lobster, mussels, red meat, and poultry. Cereals are often fortified with zinc. Most multivitamin and nutritional supplements contain zinc.

Zinc and COVID-19

The use of zinc for SARS-CoV-2 was a topic routinely flagged by COVID fact checkers as “misinformation,” so word didn’t really get out about its potential as an anti-COVID agent. However, there are more than 35 studies that provided evidence on zinc’s promise for keeping people healthy if they get COVID.

Zinc gluconate (R), zinc acetate (R) and zinc sulphate (R) have all been shown to reduce the severity and duration of viral infections such as the common cold. Zinc also appears to be the key ingredient in treatment protocols using hydroxychloroquine (HCQ).

The reason for this is because HCQ is a zinc ionophore (zinc transport molecule), meaning it’s a drug that improves your cells’ uptake of zinc. Once inside your cells, zinc prevents viral replication. This is also why zinc and zinc ionophores need to be taken very early in the illness, or as a prophylactic.

The problem is that zinc is largely insoluble and cannot easily enter through the fatty wall of your cells. Getting all the way into the cell is crucial, as this is where the viral replication occurs. This is why zinc ionophores are so important.

Aside from hydroxychloroquine, other natural, and safer, zinc ionophores include quercetin and epigallocatechin-gallate (EGCG). If given early, zinc along with a zinc ionophore should, at least theoretically, help lower the viral load and prevent the immune system from becoming overloaded.

Check out the evidence tracker on zinc and COVID-19 from c19zinc.com (constantly updated). 

Safety: Taking zinc long term is typically safe for healthy adults, as long as the daily dose is under the set upper limit of 40 mg of elemental zinc (PubMed). Be aware that typical daily doses of zinc provided by zinc lozenges generally exceed tolerable upper limits for zinc, and for this reason, they should not be used for longer than about a week. 

Excessive doses may interfere with copper absorption, which could negatively affect your immune system as it can cause copper deficiencies, blood disorders and potentially permanent nerve damage. Zinc can also impair the absorption of antibiotics, and use of zinc nasal gels or swabs has been linked to temporary or permanent loss of smell.

When it comes to zinc supplementation, more is not necessarily better. In fact, it can frequently backfire is you do not also maintain a healthy zinc-to-copper ratio. As explained by Chris Masterjohn, who has a Ph.D. in nutritional sciences, in an article and series of Twitter posts:

“In one study, 300mg/day of zinc as two divided doses of 150 mg zinc sulfate decreased important markers of immune function, such as the ability of immune cells known as polymorphonuclear leukocytes to migrate toward and consume bacteria.

The most concerning effect in the context of COVID-19 is that it lowered the lymphocyte stimulation index 3 fold. This is a measure of the ability of T cells to increase their numbers in response to a perceived threat. The reason this is so concerning in the context of COVID-19 is that poor outcomes are associated with low lymphocytes …

The negative effect on lymphocyte proliferation found with 300 mg/day and the apparent safety in this regard of 150 mg/d suggests that the potential for hurting the immune system may begin somewhere between 150-300 mg/d …

It is quite possible that the harmful effect of 300 mg/d zinc on the lymphocyte stimulation index is mediated mostly or completely by induction of copper deficiency …

The negative effect of zinc on copper status has been shown with as little as 60 mg/d zinc. This intake lowers the activity of superoxide dismutase, an enzyme important to antioxidant defense and immune function that depends both on zinc and copper …

A study done with relatively low intakes of zinc suggested that acceptable ratios of zinc to copper range from 2:1 to 15:1 in favor of zinc. Copper appears safe to consume up to a maximum of 10 mg/d.

Notably, the maximum amount of zinc one could consume while staying in the acceptable range of zinc-to-copper ratios and also staying within the upper limit for copper is 150 mg/d.”

Another factor to keep in mind is that certain additives can inhibit zinc absorption, which is the complete opposite of what you’re looking for. For instance, research has shown citric acid, glycine, mannitol and sorbitol can reduce zinc absorption,48 so zinc lozenges containing these ingredients may be less useful.

Zinc Form and Dosage

There are several types of zinc supplements. Supplements contain several forms of zinc, including zinc gluconate, zinc citrate and zinc picolinate. The percentage of elemental zinc varies by form. To find out the percentage of elemental zinc in each form, check out elemental zinc percentage.

Chelated zinc is a general form of supplementary zinc in which the zinc is chelated — or bound — to a compound to make it easier for the body to absorb. Zinc picolinate or zinc gluconate are formed when zinc is chelated to picolinic acid or gluconic acid, so the main difference between zinc gluconate and picolinate is what compound it is bound to.

To find out which zinc supplement to consider, check out best zinc supplement.

Most people do not lack an intake of zinc, but in disease state, there might be an increase in demand by the body. The FLCCC I-Prevent protocol recommends 20 - 50 mg a day for prevention and the FLCCC I-Care protocol recommends 75 - 100 mg a day for early treatment of COVID-19. This should not be taken long term without evaluation of your zinc/copper ratios.

The ideal zinc form should come from zinc lozenges to spread the zinc through the tissues of the nose, mouth and throat. It should be accompanied by at least 1 mg copper from food and supplements for every 15 mg zinc.

Do take note that you should keep the dosage back to within 40 mg/d once the exposure risk is back to normal.

4. Vitamin C - Anti-inflammatory

Vitamin C, which most of us reach for with any cold or flu, was used in high doses to great effect by COVID-19 early treatment doctors.

Vitamin C may be one of the most well-known immune nutrients that protect against immune deficiencies and which supports the prevention and recovery from the common cold and upper-respiratory issues, and also protects your cardiovascular system, eyes, skin, and other parts of your body. Research has found that vitamin C may help to optimize the immune system.

Do take note that the vitamin C dosages given in the hospitals intravenously are different from those over the counter vitamin C supplements. Therefore, when you come across studies on vitamin C, you need to differentiate those that are given intravenously vs oral vitamin C.

Vitamin C and COVID-19

 

Check out the evidence tracker on vitamin C and COVID-19 from c19vitaminc.com (constantly updated).

Safety: The U.S. Recommended Dietary Allowance (RDA) for vitamin C is 75 to 120 milligrams per day. Taking large doses of vitamin C (ascorbic acid) on a regular basis lowers your level of copper, so if you are already deficient in copper and take high doses of vitamin C, you can compromise your immune system.

While generally considered safe even in high doses, way too much vitamin C — anything above 2,000 milligrams daily—can cause headaches, insomnia, diarrhea, heartburn, and other issues.

Be aware that there are side effects and risks associated with taking high doses of vitamin C. People sometimes assume there is no harm in taking large doses because vitamin C is water-soluble (i.e. excess vitamin C is excreted from the body), but this is not the case. In addition to causing gastric distress and diarrhea, high doses of vitamin C (over 500 mg per day) over the long-term may increase the risk of cataracts. High-dose vitamin C can also reduce the effectiveness of certain medications and interfere with certain blood tests. Furthermore, very high-dose vitamin C (typically 2,000 mg per day or more) can increase the risk of oxalate nephropathy — a condition in which oxalate crystals are deposited in the kidney, leading to kidney damage and/or kidney failure. Cases of this were shown to rise during the first two years of the COVID-19 pandemic, likely due to increased use of very high dose vitamin C (Fong, Kidney Int Rep 2022).

That said, temporarily taking megadoses of vitamin C supplements to combat a case of the cold or flu is likely not going to cause a problem.

Many vitamin C supplements that are above the US RDA are sold in the market. It’s important to seek a physician’s advice if you intend to take high dose vitamin C on a long term basis. To be on the safe side, you may also request for your kidney functions to be monitored.

For long-term, daily use, your best bet is to eat a diet that is full of high quality organic vegetables and fruits that are minimally processed. Not only will you get vitamin C, but you will get all the other accessory nutrients and micronutrients that are needed to optimize it. 

Vitamin C, Omicron and Deltacron

Will Vitamin C Work Against Omicron variants? Vitamin C is not variant specific because it's primary mode of action is to support the body’s immune system which reacts in a variety of ways against viral attack, not just in a specific antibody reaction to a specific spike protein. 

Related: Best Vitamin C Supplement

Quercetin, Vitamin C, Zinc and Vitamin D3

What are right doses for zinc, quercetin, vitamin C and vitamin D3? The FLCCC I-MASK+ prevention and treatment protocols have the recommended doses depending on whether you are taking them for prevention or treatment.

For updated prevention and early outpatient protocol  for COVID-19 positive, please check out FLCCC I-MASK+ protocol.

Related References:

• Quercetin Inhibits Influenza Infection [1]
• Quercetin Performs Inhibitory Activity in the Initial Stage of Influenza Virus [1]
• Quercetin: Antiviral Significance and Possible COVID-19 Integrative Considerations [2]
• Quercetin: A Promising Treatment for the Common Cold [3]
• Quercetin has Potent Anti-Cold (HRV2) Activity [4]
• Quercetin is a Strong and Long Lasting Anti-Inflammatory [5]
• Quercetin as a Promising Therapeutic Strategy for Chronic Disease Management [6]
• Quercetin Inhibits the Interaction Between Virus-Cell Link in Influenza [7]
• Quercetin Combined with Zinc Provides Powerful Zinc Ionophores [7]
• Zinc Ionophores have Anti-Cancer Properties [7]
• Quercetin and Vitamin C Demonstrated Synergistic Prophylactic and Treatment Evidence for COVID-19 [8]
• Quercetin and Vitamin D as Possible COVID-19 Mitigation Agents [9]
• Flavonoids Inhibit SARS-CoV 3CL Protease [10]
• Flavonoids as Potent MERS-CoV 3C-like Proteasee Inhibitors [11]
• Zinc Possesses Unique and Distinct Antiviral Properties Against a Number of Human Viruses [12]
• Zinc has been Shown to Contribute to a Number of Innate and Adaptive Immune Signaling Pathways [12]
• Upon Recognition of Microbial Antigens, a Rapid and Transient Influx of Free Zinc Occurs[12]
• Zinc Plays a Significant Role in the Response to [Interferons] by Modulating Secretion, Cytokine Potency, and Receptor Binding, as well as Influencing Signaling Intermediates and Pathway Inhibitors [12]
• Zinc Deficiency can probably be added to the Factors Predisposing Individuals to Infection and Detrimental Progression of COVID-19 [13]
• Zinc has Direct Antiviral Effects as Demonstrated in Various Cases. Examples Include Coronaviridae [i.e. Coronaviruses] [13]
• Zinc Supplementation Improves the Mucociliary Clearance, Strengthens the Integrity of the Epithelium, Decreases Viral Replication, Preserves Antiviral Immunity, Attenuates the Risk of Hyper-Inflammation, Supports Anti-Oxidative Effects and thus Reduces Lung Damage and Minimized Secondary Infections [13]
• Vitamin D Significantly Reduces the Need for ICU Treatment for COVID-19 Patients [14]
• Vitamin D Appears to Reduce the Severity of COVID-19 [14]
• Randomised Controlled Trials Showed that Vitamin D Decreases Acute Respiratory Infections (ARIs) [15]
• Low Vitamin D Status Might be Associated with an Increased Risk of COVID-19 Infection [16]
• Preliminary Observational Studies Indicate Low Vitamin C Status in Critically Ill Patients with COVID-19 [17]
• Possible Therapeutic Effects of Adjuvant Quercetin Supplementation Against Early-Stage COVID-19 Infection [18]
• Quercetin is a powerful senolytic, inducing death of senescent cells and improving overall health [19]
• In preclinical models, Quercetin delays, prevents or alleviates frailty, cancers and cardiovascular, neuropsychiatric, liver, kidney, musculoskeletal, lung, eye, hematological, metabolic and skin disorders as well as complications of organ transplantation, radiation and cancer treatment [19]
• Quercetin as possible anti-aging therapy [19]
• Quercetin disaggregates prion fibrils and reduces fibril-Induced cytotoxicity and oxidize stress, thus reducing spike protein induced diseases such as Alzheimer's, Lewey Body Dementia, Mad Cow, etc. [20]
• Quercetin has properties that disaggregate fibrils, and in conjunction with Serratiopeptidase which breaks down the disaggregated fibril waste may be useful in COVID-19 [21]
• Bromelain inhibits SARS-CoV-2 infection via targeting of ACE-2, TMPRSS2, and spike protein [22]
• Bromelain may be a powerful antiviral against SARS-CoV-2 and future coronaviruses [22]

Related: 

• Best Zinc Quercetin Supplement

• Best Vitamin D3 Supplements 2024

• Vitamins and Supplements Guide

• Best Zinc Supplements 2024